Effects of ketocyclazocine and ethylketocyclazocine on electric shock titration

The effects of two putative kappa agonists, ketocyclazocine and ethylketocyclazocine, on electric shock titration in squirrel monkeys were determined. Drugs were tested alone, in combination with naloxone and following the development of morphine tolerance. Both ketocyclazocine and ethylketocyclazocine produced biphasic dose-effect curves. Low doses decreased whereas high doses increased the intensity at which monkeys maintained the shock. Naloxone antagonized the effects of ketocyclazocine and ethylketocyclazocine; however, the dose of naloxone required to antagonize their effects was much larger than the dose required to antagonize equivalent effects of morphine. When the effects of ethylketocyclazocine were redetermined in monkeys tolerant to morphine, the ethylketocyclazocine dose-effect curve was shifted to the left whereas the morphine curve was shifted to the right. It was concluded that the effects of the kappa agonists can be differentiated from morphine by the shape of their dose-effect curve, the ease with which they are antagonized by naloxone and the lack of cross tolerance to morphine.